{2-[(Methanesulfonyl)amino]phenyl}boronic acid → HCID 90312625, compound

HRID 1523966Notes

Reaction equation

HRID 1523966 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)=[C:4]([F:15])[C:3]=1[CH3:16].[CH3:17][S:18]([NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O)(=[O:20])=[O:19]>CC(C1C=C(C(C)C)C(C2C=CC=C(P(C3CCCCC3)C3CCCCC3)C=2)=C(C(C)C)C=1)C.C1C=[C-]C(C2C(N)=CC=CC=2)=CC=1.Cl[Pd+]>[NH2:14][C:11]1[N:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[NH:21][S:18]([CH3:17])(=[O:20])=[O:19])=[C:3]([CH3:16])[C:4]=2[F:15])=[N:9][CH:10]=1

Participants

4

Reactant 2

HCID 2773533{2-[(Methanesulfonyl)amino]phenyl}boronic acidHCID 90314391HCID 90314391, compound

Product 1

HCID 90312625HCID 90312625, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 72376365[2-(2-Aminophenyl)phenyl]-chloro-palladium dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphaneCatalyst

Procedure

To a mixture of 5-(4-chloro-2-fluoro-3-methylphenyl)pyrazin-2-amine (75 mg, 0.32 mmol), (2-(methylsulfonamido)phenyl)boronic acid (85 mg, 0.39 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (5.0 mg, 0.006 mmol) in a sealed tube flushed with N2 were added N2 sparged K3PO4 (1.26 ml, 0.5 N) followed by N2 sparged THF (0.63 ml). The reaction mixture was stirred at rt for 18 hours. The reaction mixture was then partitioned between EtOAc and brine. The organic layer was isolated, dried over MgSO4, filtered and concentrated to dryness. Purification by FCC afforded the title compound (100 mg, 85%). MS (ESI): mass calcd. for C18H17FN4O2S, 372.10; m/z found, 373.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.39-8.35 (m, 1H), 8.02 (d, J=1.5, 1H), 7.70 (m, 1H), 7.47 (dd, J=8.1, 1.0, 1H), 7.45-7.39 (m, 1H), 7.29 (m, 1H), 7.21 (dd, J=7.6, 1.5, 1H), 7.07 (d, J=8.0, 1H), 6.67 (s, 2H), 2.87 (s, 3H), 2.01 (d, J=2.5, 3H).

Workup

  1. customflushed with N2
  2. additionwere added N2
  3. customsparged K3PO4 (1.26 ml, 0.5 N)
  4. customsparged THF (0.63 ml)
  5. customThe reaction mixture was then partitioned between EtOAc and brine
  6. customThe organic layer was isolated
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customPurification by FCC

Sources & evidence

ORD record
ord-6c9521db74bc4b7285431871670359b9
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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